Psychiatric Exacerbations and Acute Stressors

https://cole-brokamp.github.io/peas

Cole Brokamp

Cincinnati Children’s Hospital Medical Center

2024-10-24

Timing of Early Life Exposures is Important

Psychiatric disorders in children and adolescents…

  • NSCH estimates 1 in 6 youth aged 6-17 have a ‘treatable mental health condition’
  • Meta-analytic estimates: 50% of all lifetime mental illnesses begin by age 14; 75% by age 25

… are psychiatric disorders across the lifespan and the population

  • Symptoms interfere with healthy social, emotional, and educational milestones
  • Causes difficulties later in life, including poor educational achievement, recurrent unemployment, substance abuse, relationship difficulties, and further psychopathology, including psychiatric crises

Early-life windows sensitive to airborne lead exposure associated with adolescent problematic behavior

  • Urban air still contains lead, although ten times lower than the current EPA standards
  • Prospective cohort study of 263 children followed from birth until age twelve (CCAAPS, PI: Ryan)
  • Monthly ambient lead associated with behavioral problems independently of maternal education, community material deprivation, blood lead concentrations, nearby greenness, and traffic

Timing during pregnancy

Parikh M, Brokamp C, Rasnick E, Ding L, Mersha TB, Bowers K, Folger AT. Epigenome-wide association of neonatal methylation and trimester-specific prenatal PM2.5 exposure. Environmental Epidemiology. 2022.

  • cg18705808 associated with the average PM2.5
  • pathway & network analysis = little similarity between first two trimesters
  • TMEM184A, the gene regulated by cg18705808, involved in inflammatory pathways

Parikh MN, Manning ER, Niu L, Ruehlmann AK, Folger AT, Brunst KJ, Brokamp C. Increasing Temporal Sensitivity of Omics Association Studies with Epigenome-Wide Distributed Lag Models. American Journal of Epidemiology. In Press. 2024.

  • New method for screening timing-specific effects in high dimensional settings: traditional false discovery rate methods + distributed lag model (DLM)
  • Achieved increased sensitivity for associations limited to specific periods of time compared to traditional two-stage approaches
  • Real-world analysis: DNAm at 353 CpG sites measured at age 12 were significantly associated with PM2.5 exposure during distinct weeks of pregnancy

Air pollution is a potentially-modifiable, population-level contributor to psychiatric morbidity

Air pollution affects the brain and central nervous system

Air pollution and public health

Particulate matter: \(PM_{10}\), \(PM_{2.5}\), and \(PM_{0.1}\); anthropogenic fuel combustion, landscape fire smoke, secondary formation of particles from precursors, windblown dust

Ozone: Secondary formation through chemical reaction of precursors with sunlight

NO\(_2\): Anthropogenic fuel combustion for transportation, electricity generation, industrial processes

EPA National Ambient Air Quality Standards

Place-based exposures and blood biomarkers of inflammation

Anxiety Symptom Severity/Frequency and Daily \(PM_{2.5}\)

  • 23 adolescents with severe generalied anxiety disorder followed over eight weeks
  • 123 total weekly pediatric anxiety rating scale (PARS) clinical assessments

Psychiatric Exacerbations

Pediatric Psychiatric Exacerbations → Hospitalizations are Increasing

  • 2009 - 2019: 26% increase in mental health hospitalizations nationwide
  • 163% in pediatric hospitalizations with a diagnosis of suicide or self-injury
  • 2019 - 2021 CDC youth survey estimates 18% of persons aged 14 to 18 completed non-suicidal self-injury

Climate and Environmental Daily Stressors

High-resolution and spatiotemporal exposure assessment models for:

  • Ambient air pollution: PM2.5, Ozone, NO2 (wildfire smoke plumes)
  • Heat: heat waves, extreme temperature, humidity, precipitation
  • Allergens: pollen, mold, ragweed

Case-Control Crossover Study Design

  • Estimate causal effects of transient treatments on acute outcomes
  • EHR-based cohort + place-based exposures advantages
  • Within-individual design prevents confounding by ‘time-invariant’ (e.g. within a month) characteristics
  • Stratification on year, month, day of week prevents confounding by temporal trends
  • Conditional logistic regression; person-time unit of observation
  • Statistical adjustment for common confounders (temperature, humidity, holidays, secular or periodic trends)

Daily PM2.5 and 13,176 CCHMC Psychiatric Encounters Between 2011 and 2015

  • Increased PM2.5 associated with increased risk one (7% [2, 12]) and two (5% [0, 10]) days later
    • Adjustment disorder and suicidality increased risk one day later
    • Stronger associations in highly deprived communities for anxiety and suicidality
    • Weaker associations in highly deprived communities for adjustment disorder

Updated CCHMC ED/UC Psychiatric Exacerbations among Hamilton County, Ohio patients, July 2016 - July 2022

Psychiatric category N visits Public ins. High com. dep.
All 12,767 8,442 (66%) 8,842 (66%)
Adjustment disorder 1,979 1,202 (61%) 562 (28%)
Anxiety disorder 1,122 529 (47%) 267 (24%)
Depressive disorder 1,636 903 (55%) 377 (23%)
Externalizing disorder 2,376 1,692 (71%) 843 (35%)
Intermittent explosive disorder 1,420 1,107 (78%) 485 (35%)
Suicide and self-inflicted injury 1,002 585 (58%) 261 (26%)
  • Odds of a psychiatric exacerbation were increased 8% (odds ratio: 1.08, 95% CI: [1.00, 1.16]) two days after a 10 \(\mu g / m^3\) increase in PM2.5
  • Driven by associations with anxiety disorders (OR 1.68, [1.06, 2.67]) and depression disorders (OR 1.20, [0.99, 1.46])

Daily \(PM_{2.5}\) increases individual-level risk of psychiatric emergency care differently by susceptibility characteristics

Individual-level, Hyperlocal, Daily Exacerbation Risk

Address Linkage

  • Fuzzy linkage of billing addresses to county parcel identifiers facilitates linkage of parcel characteristics from auditors webpage and enforced housing infractions from Open Data Cincinnati
  • parcel, shotspotter, violent crime, HUD, auditor

Longitudinal Residential History in an EHR-based Prospective Cohort

  • Registry of children utilizing CCHMC ED/UC for asthma July 2016 - July 2022
  • Prospectively follow 13,404 asthma patients living at 22,762 unique addresses for 11 million cumulative patient-days

Exacerbations associated with poor housing conditions

  • 9.9% experienced an exacerbation
  • 12% exposed to poor housing conditions
  • proportional hazards model adjusted for public insurance and total market value by housing type
  • living at a parcel with a housing infraction during the previous year associated with 34% (95% CI: 8% to 67%) increased exacerbation risk

Population’s Unified Life Stress Evaluation

Temporal measures of collective mental health and well-being among the population served by CCHMC:

  • Number of mass shooting (National Gun Violence Archive)
  • Suicide, suicidality, non-suicidal self-injury rates
  • Neighborhood-level rates of acute mental health crises reported in healthcare settings
  • Trends in anxiety and depression keywords from social media and search engines
  • Pulse surveys and public sentiments
  • AQI, heat waves, pollen, mold
  • Cincy Air Watch
  • Gun violence, violent crime, gunshots
  • Housing infractions, eviction filings
  • Alleged child abuse and neglect rates
  • Food insecurity
  • Civic engagement